Public Assessment Report. Decentralised Procedure
|
|
- Claire Whitehead
- 7 years ago
- Views:
Transcription
1 Public Assessment Report Decentralised Procedure Levodopa/Carbidopa/Entacapone Accord 100 mg/25 mg/200 mg Film-coated tablets Levodopa/Carbidopa/Entacapone Accord 150 mg/37.5 mg/200 mg Film-coated tablets Levodopa/Carbidopa/Entacapone Accord 125 mg/31.25 mg/200 mg Film-coated tablets Levodopa/Carbidopa/Entacapone Accord 200 mg/50 mg/200 mg Film-coated tablets Levodopa/Carbidopa/Entacapone Accord 50 mg/12.5 mg/200 mg Film-coated tablets Levodopa/Carbidopa/Entacapone Accord 75 mg/18.75 mg/200 mg Film-coated tablets (Levodopa, carbidopa and entacapone) Procedure No: UK Licence No: PL 20075/ Accord Healthcare Limited 1
2 LAY SUMMARY Levodopa/Carbidopa/Entacapone Accord 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50 mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg Film-coated tablets (levodopa, carbidopa and entacapone) The products Levodopa/Carbidopa/Entacapone Accord 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets may be referred to as Levodopa/Carbidopa/Entacapone Accord film-coated tablets this report. This is a summary of the Public Assessment Report (PAR) for Levodopa/Carbidopa/Entacapone Accord 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50 mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets (PL 20075/ ; ). It explains how Levodopa/Carbidopa/Entacapone Accord film-coated tablets were assessed and their authorisation recommended, as well as their conditions of use. It is not intended to provide practical advice on how to use Levodopa/Carbidopa/Entacapone Accord film-coated tablets. For practical information about using Levodopa/Carbidopa/Entacapone Accord film-coated tablets patients should read the package leaflet or contact their doctor or pharmacist. What are Levodopa/Carbidopa/Entacapone Accord film-coated tablets and what are they used for? Levodopa/Carbidopa/Entacapone Accord film-coated tablets are generic medicines. This means that Levodopa/Carbidopa/Entacapone Accord film-coated tablets are similar to reference medicines already authorised in the European Union (EU) called Stalevo 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets (Orion Corporation, Finland). Stalevo 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets may be referred to as Stalevo film-coated tablets in this report. Levodopa/Carbidopa/Entacapone Accord film-coated tablets are used for the treatment of Parkinson s disease. How do Levodopa/Carbidopa/Entacapone Accord film-coated tablets work? Parkinson s disease is caused by low levels of a substance called dopamine in the brain. Levodopa/Carbidopa/Entacapone Accord film-coated tablets contain three active substances (levodopa, carbidopa and entacapone) in each film-coated tablet. Levodopa increases the amount of dopamine and hence reduces the symptoms of Parkinson s disease. Carbidopa and entacapone improve the antiparkinson effects of levodopa. 2
3 How are Levodopa/Carbidopa/Entacapone Accord film-coated tablets used? Levodopa/Carbidopa/Entacapone Accord film-coated tablets are taken by mouth. Levodopa/Carbidopa/Entacapone Accord film-coated tablets can only be obtained with a prescription. The tablets should be taken exactly as told by the doctor or pharmacist. The patient should check with the doctor or pharmacist if not sure. For adults and elderly: The patient s doctor will tell the patient exactly how many tablets of this medicine to take each day. The tablets are not intended to be split or broken into smaller pieces. The patient should take only one tablet each time. Depending on how the patient responds to treatment, the patient s doctor may suggest a higher or lower dose. If the patient is taking Levodopa/Carbidopa/Entacapone Accord 50 mg/12.5 mg/200 mg, 75 mg/18.75 mg/200 mg, 100 mg/25 mg/200 mg, 125 mg/31.25 mg/200 mg or 150 mg/37.5 mg/200 mg tablets, no more than 10 tablets per day should be taken. If the patient is taking Levodopa/Carbidopa/Entacapone Accord 200 mg/50 mg/200 mg, he/she should not take more than 7 tablets of this strength per day. The patient should speak to the doctor or pharmacist if he/she thinks the effect of this medicine is too strong or too weak, or if he/she experiences possible side effects. For further information on how Levodopa/Carbidopa/Entacapone Accord film-coated tablets are used, please refer to the package leaflet and Summaries of Product Characteristics available on the Medicines and Healthcare products Regulatory Agency (MHRA) website. What benefits of Levodopa/Carbidopa/Entacapone Accord film-coated tablets have been shown in studies? As Levodopa/Carbidopa/Entacapone film-coated tablets are generic medicines, studies in patients have been limited to tests to determine that Levodopa/Carbidopa/Entacapone Accord 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets are bioequivalent to the reference medicines, Stalevo 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets, respectively. Two medicines are bioequivalent when they produce the same levels of the active substance in the body. In addition, the Marketing Authorisation Holder (Accord Healthcare Limited) provided data from the published literature on levodopa, carbidopa and entacapone. What are the possible side effects of Levodopa/Carbidopa/Entacapone Accord film-coated tablets? Because Levodopa/Carbidopa/Entacapone Accord film-coated tablets are generic medicines and are bioequivalent to the reference medicines Stalevo film-coated tablets (Orion Corporation, Finland), the possible side effects are taken as being the same as those of the reference medicines. For the full list of restrictions, see the package leaflet available on the MHRA website. 3
4 Why are Levodopa/Carbidopa/Entacapone Accord film-coated tablets approved? It was concluded that, in accordance with EU requirements, Levodopa/Carbidopa/Entacapone Accord film-coated tablets have been shown to have comparable quality and to be bioequivalent to Stalevo film-coated tablets (Orion Corporation, Finland). Therefore, the view was that, as for Stalevo film-coated tablets (Orion Corporation, Finland), the benefits outweighs the identified risks. What measures are being taken to ensure the safe and effective use of Levodopa/Carbidopa/Entacapone Accord film-coated tablets? A Risk Management Plan has been developed to ensure that Levodopa/Carbidopa/Entacapone Accord film-coated tablets are used as safely as possible. Based on this plan, safety information has been included in the Summaries of Product Characteristics and the package leaflet for Levodopa/Carbidopa/Entacapone Accord film-coated tablets, including the appropriate precautions to be followed by healthcare professionals and patients. Known side effects are continuously monitored. Furthermore new safety signals reported by patients and healthcare professionals will be monitored and reviewed continuously as well. Other information about Levodopa/Carbidopa/Entacapone Accord film-coated tablets Austria (PL 20075/0417-8; UK/H/5908/ /DC and PL 20075/0421; UK/H/5908/005/DC only), Cyprus, Denmark, Finland, France, Italy, Malta, The Netherlands, Sweden and the UK agreed to grant Marketing Authorisations for Levodopa/Carbidopa/Entacapone Accord film-coated tablets on 04 December Marketing Authorisations were granted in the UK to Accord Healthcare Limited on 23 December The full PAR for Levodopa/Carbidopa/Entacapone Accord film-coated tablets follows this summary. For more information about treatment with Levodopa/Carbidopa/Entacapone Accord film-coated tablets, read the package leaflet, or contact your doctor or pharmacist. This summary was last updated in February
5 SCIENTIFIC DISCUSSION TABLE OF CONTENTS I Introduction Page 6 II Quality aspects Page 7 III Non-clinical aspects Page 24 IV Clinical aspects Page 24 V User consultation Page 30 VI Overall conclusion, benefit/risk assessment and Page 30 recommendation Annex 1 - Table of content of the PAR update for MRP and DCP Page 32 5
6 Scientific discussion I INTRODUCTION Based on the review of the data on quality, safety and efficacy, the Member States considered that the applications for Levodopa/Carbidopa/Entacapone Accord 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets (PL 20075/ ; ) could be approved. These are prescription-only medicines (POM) indicated for the treatment of adult patients with Parkinson s disease and end-of-dose motor fluctuations not stabilised on levodopa/dopa decarboxylase (DDC) inhibitor treatment. The products may be referred to as Levodopa/Carbidopa/Entacapone Accord film-coated tablets in this report. These applications were submitted using the Decentralised Procedure (DCP), with the UK as Reference Member State (RMS), and Austria (Procedures UK/H/5908/ /DC and UK/H/5908/005/DC only), only), Cyprus, Denmark, Finland, France, Italy, Malta, The Netherlands and Sweden as Concerned Member States (CMS). The applications were submitted under Article 10(1) of Directive 2001/83/EC, as amended, claiming to be generic medicinal products of the originator medicinal products Stalevo 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets (Orion Corporation, Finland) which were authorised in the EEA via the Centralised Procedure. Stalevo 50 mg/12.5 mg/200 mg, 100 mg/25 mg/200 mg, 150mg/37.5 mg /200 mg and 200 mg/50 mg/200 mg film-coated tablets were authorised on 17 October Stalevo 75 mg/18.75 mg/200 mg and 125 mg/31.25 mg/200 mg film-coated tablets were authorised on 27 March 2009, as extension applications for new dosage strengths to the existing Marketing Authorisations for Stalevo film-coated tablets authorised on 17 October The active ingredients in these products are levodopa, carbidopa and entacapone. Levodopa mediates the antiparkinsonian effect whereas carbidopa and entacapone inhibit the peripheral metabolism of levodopa. Levodopa is a precursor of dopamine and is given as replacement therapy in Parkinson's disease. Carbidopa is a peripheral dopa decarboxylase inhibitor. It prevents metabolism of levodopa to dopamine in the peripheral circulation, ensuring that a higher proportion of the dose reaches the brain, where dopamine acts. A lower dose of levodopa can be used, reducing the incidence and severity of side effects. Entacapone is a reversible, specific and mainly peripherally acting catechol-o-methyltransferase (COMT) inhibitor.entacapone decreases the metabolic loss of levodopa to 3 O-methyldopa (3-OMD) mainly in peripheral tissues. The amount of levodopa available to the brain is increased, thus prolongs the clinical response to levodopa. Three bioequivalence studies were submitted to support these applications; two bioequivalence studies comparing the applicant s test Fixed Drug Formulation (FDC) of Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg tablet with the reference product Stalevo tablets containing Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg (Orion Pharma GmbH, Germany), under fasting conditions and one bioequivalence study comparing the applicant s test product FDC of Levodopa 50 mg, Carbidopa 12.5 mg and Entacapone 200 mg tablet versus the reference product Stalevo tablets containing Levodopa 50 mg, Carbidopa 12.5 mg and Entacapone 200 mg (Orion Corporation, Finland) 6
7 under fasting conditions. The bioequivalence studies were carried out in accordance with Good Clinical Practice (GCP). With the exception of the bioequivalence studies, no new non-clinical or clinical data were submitted, which is acceptable given that the applications were based on being generic medicinal products of originator products that have been in clinical use for over 10 years. The RMS has been assured that acceptable standards of Good Manufacturing Practice (GMP) are in place at all sites responsible for the manufacture, assembly and batch release of these products. For manufacturing sites within the Community, the RMS has accepted copies of current manufacturing authorisations issued by inspection services of the competent authorities as certification that acceptable standards of GMP are in place at those sites. For manufacturing sites outside the Community, the RMS has accepted copies of current GMP Certificates of satisfactory inspection summary reports, close-out letters or exchange of information issued by the inspection services of the competent authorities (or those countries with which the EEA has a Mutual Recognition Agreement for their own territories) as certification that acceptable standards of GMP are in place at those non-community sites. The Member States considered that the applications could be approved at the end of procedure (Day 210) on 04 December After a subsequent national phase, licences were granted in the UK to Accord Healthcare Limited on 23 December II QUALITY ASPECTS II.1 INTRODUCTION The submitted documentation concerning the proposed product is of sufficient quality and meets the current EU regulatory requirements. The quality overall summary has been written by an appropriately qualified person and is a suitable summary of the pharmaceutical aspects of the dossier. Description and composition 1. Levodopa/Carbidopa/Entacapone 100 mg/25 mg/200 mg strength tablets are light brown to greyish-red coloured, oval-shaped approximately 16.7 mm in width, film-coated with debossed with 100 on one side, and plain on the other. Each Levodopa/Carbidopa/Entacapone 100 mg/25 mg/200 mg tablet contains 100 mg of levodopa, 25 mg of carbidopa and 200 mg of entacapone. 2. Levodopa/Carbidopa/Entacapone 150 mg/37.5 mg/200 mg strength tablets are light brown to grayish red coloured, elongated-ellipse shaped, approximately 16.2 mm in length and 10.2 mm in width and film-coated with debossed 150 on one side and plain on other side. Each Levodopa/Carbidopa/Entacapone 150 mg/37.5 mg/200 mg tablet contains 150 mg of levodopa, 37.5 mg of carbidopa and 200 mg of entacapone. 3. Levodopa/Carbidopa/Entacapone 125 mg/31.25 mg/200 mg strength tablets are light brown to light pink coloured, elongated-ellipse shaped, approximately 15.2 mm in length and 9.7 mm in width and film-coated with debossed 125 on one side and plain on other side. Each Levodopa/Carbidopa/Entacapone 125 mg/31.25 mg/200 mg tablet contains 125 mg of levodopa, mg of carbidopa and 200 mg of entacapone. 7
8 4. Levodopa/Carbidopa/Entacapone 200 mg/50 mg/200 mg strength tablets are dark brownish red coloured, oval shaped, approximately mm in length and 9.05 mm in width and film-coated with debossed "200" on one side and plain on other side. Each Levodopa/Carbidopa/Entacapone 200 mg/50 mg/200 mg tablet contains 200 mg of levodopa, 50 mg of carbidopa and 200 mg of entacapone. 5. Levodopa/Carbidopa/Entacapone 50 mg/12.5 mg/200 mg strength tablets are light brown to grayish red coloured, round, approximately 11.3 mm in diameter, biconvex and film-coated with debossed 50 on one side and plain on other side. Each Levodopa/Carbidopa/Entacapone 50 mg/12.5 mg/200 mg tablet contains 50 mg of levodopa, 12.5 mg of carbidopa and 200 mg of entacapone. 6. Levodopa/Carbidopa/Entacapone 75 mg/18.75 mg/200 mg strength tablets are light brown to light pink coloured, oval shaped, approximately 15.2 mm in length and 7.2 mm in width and film-coated with debossed 75 on one side and plain on other side. Each Levodopa/Carbidopa/Entacapone 75 mg/18.75 mg/200 mg contains 75 mg of levodopa, mg of carbidopa and 200 mg of entacapone. The products also contain pharmaceutical excipients in the tablet cores and coatings, namely microcrystalline cellulose, crospovidone (Type B), Povidone K-30, magnesium stearate, sodium citrate, hypromellose, macrogol 6000, titanium dioxide (E171), polysorbate 80 and red iron oxide (E172). In addition, Levodopa/Carbidopa/Entacapone Accord 50 mg/12.5 mg/200 mg, 100 mg/25 mg /200 mg and 150 mg/37.5 mg/200 mg film-coated tablets contain yellow iron oxide (E172). Appropriate justification for the inclusion of each excipient has been provided. With the exception of red iron oxide (E172) and yellow iron oxide (E172), all excipients comply with their respective European Pharmacopoeia monographs. Red iron oxide (E172) and yellow iron oxide (E172) are in compliance with the current EU Directive concerning the use of colouring agents. None of the excipients contain materials of animal or human origin. No genetically modified organisms (GMO) have been used in the preparation of these excipients. The products are packaged in high-density polyethylene (HDPE) bottles, with child-resistant polypropylene closures. Each HDPE bottle contains 1 silica gel canister closures. The products are available in pack sizes of 30, 100 and 130 tablets film-coated tablets. Not all pack sizes may be marketed. Satisfactory specifications and Certificates of Analysis have been provided for all packaging components. All primary packaging complies with current European regulations concerning materials in contact with foodstuff. 8
9 II.2 DRUG SUBSTANCE LEVODOPA INN: Levodopa Chemical name: (2S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid Molecular formula: C 9 H 11 NO 4 Structure: Mr: Appearance: White or almost white, crystalline powder. Solubility: Slightly soluble in water, practically insoluble in ethanol (96 per cent). It is freely soluble in 1 M hydrochloric acid and sparingly soluble in 0.1 M hydrochloric acid. Levodopa is the subject of a European Pharmacopoeia monograph. All aspects of the manufacture and control of the active substance, levodopa, are covered by a European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate of Suitability. DRUG SUBSTANCE - CARBIDOPA INN: Carbidopa Chemical name: (2S)-3-(3,4-Dihydroxyphenyl)-2-hydrazino-2-methylpropanoic acid monohydrate Molecular formula: C 10 H 14 N 2 O 4, H 2 O Structure: Mr: Appearance: White or yellowish-white powder. Solubility: Slightly soluble in water, very slightly soluble in ethanol (96 per cent), practically insoluble in methylene chloride. It dissolves in dilute solutions of mineral acids. Carbidopa is the subject of a European Pharmacopoeia monograph. All aspects of the manufacture and control of the active substance, carbidopa, are covered by a European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate of Suitability. DRUG SUBSTANCE - ENTACAPONE INN: Entacapone Chemical name: (2E)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2- enamide Molecular formula: C 14 H 15 N 3 O 5 9
10 Structure: Mr: Appearance: A greenish yellow or yellow powder. Solubility: Practically insoluble in water, soluble or sparingly soluble in acetone, and slightly soluble in anhydrous ethanol. Entacapone is the subject of a European Pharmacopoeia monograph. All aspects of the manufacture and control of the active substance, entacapone, are covered by a European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate of Suitability. II.3 MEDICINAL PRODUCT Pharmaceutical Development The objective of the development programme was to formulate safe, efficacious, stable film-coated tablets containing levodopa, carbidopa and entacapone, which were bioequivalent to Stalevo 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets (Orion Corporation, Finland). Suitable pharmaceutical development data have been provided for these applications. Comparative in-vitro dissolution and impurity profiles have been provided for these products and the respective reference products Stalevo 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets (Orion Pharma, Finland). The dissolution and impurity profiles were satisfactory. Manufacturing Process Satisfactory batch formulae have been provided for the manufacture of the products, along with an appropriate account of the manufacturing process. Based on production-scale/near to production-scale batches, the manufacturing process has been validated and has shown satisfactory results. The Marketing Authorisation holder has committed to performing process validation on future production-scale batches. Control of Finished Product The finished product specifications are acceptable. Test methods have been described and have been validated adequately. Batch data have been provided and comply with the release specifications. Certificates of Analysis have been provided for all working standards used. Stability of the Product Finished product stability studies were performed in accordance with current guidelines on batches of finished product in the packaging proposed for marketing. Based on the results, the following shelf-lives have been accepted: - 3 years for product packaged in in unopened HDPE bottles. - 6 months after first opening, for product in opened HDPE bottles. There are no special temperature storage conditions required for the products. Suitable post approval stability commitments have been provided to continue stability testing on batches of finished product. 10
11 Bioequivalence/Bioavailability Satisfactory Certificates of Analysis have been provided for the test and reference batches used in the bioequivalence studies. The bioequivalence studies are discussed in Section III.3, Clinical Aspects. II.4 Discussion on chemical, pharmaceutical and biological aspects It is recommended that Marketing Authorisations are granted for Levodopa/Carbidopa/Entacapone Accord film-coated tablets, from a quality point of view. II.5 Summary of Product Characteristics (SmPCs), Patient Information Leaflets (PILs) and Labels The SmPCs, PILs and labelling text are satisfactory and, where appropriate, in line with current guidance. In accordance with Directive 2010/84/EU, the current version of the SmPCs and PILs are available on the MHRA website. The current labelling is presented below: 11
12 Levodopa/Carbidopa/Entacapone Accord 100 mg/25 mg/200 mg film-coated tablets: 12
13 13
14 Levodopa/Carbidopa/Entacapone Accord 150 mg/37.5 mg/200 mg film-coated tablets: 14
15 15
16 Levodopa/Carbidopa/Entacapone Accord 125 mg/31.25 mg/200 mg film-coated tablets: 16
17 17
18 Levodopa/Carbidopa/Entacapone Accord 200 mg/50 mg/200 mg film-coated tablets: 18
19 19
20 Levodopa/Carbidopa/Entacapone Accord 50 mg/12.5 mg/200 mg film-coated tablets: 20
21 21
22 Levodopa/Carbidopa/Entacapone Accord 75 mg/18.75 mg/200 mg film-coated tablets: 22
23 23
24 III. NON-CLINICAL ASPECTS III.1 Introduction As the pharmacodynamic, pharmacokinetic and toxicological properties of levodopa, carbidopa and entacapone are well-known, no new non-clinical data are required and none have been provided. The non-clinical overview has been written by an appropriately qualified person and is satisfactory, providing an appropriate review of the relevant non-clinical pharmacology, pharmacokinetics and toxicology. III.2 Pharmacology Not applicable, see Section III.1 Introduction, above. III.3 Pharmacokinetics Not applicable, see Section III.1 Introduction, above. III.4 Toxicology Not applicable, see Section III.1 Introduction, above. III.5 Ecotoxicity/Environmental Risk Assessment (ERA) The Marketing Authorisation Holder has provided adequate justification for not submitting an Environment Risk Assessment (ERA). As the applications are for generic versions of already authorised products, it is not expected that environmental exposure will increase following approval of the Marketing Authorisations for the proposed products. An environmental risk assessment is therefore not deemed necessary. III.6 Discussion of the non-clinical aspects No new non-clinical studies were conducted, which is acceptable given that the applications were based on being generic medicinal products of an originator product that has been licensed for over 10 years. It is recommended that Marketing Authorisations are granted for Levodopa/Carbidopa/Entacapone Accord film-coated tablets, from a non-clinical point of view. IV. CLINICAL ASPECTS IV.1 Pharmacokinetics The clinical pharmacology of levodopa, carbidopa and entacapone is well-known. With the exception of data from the bioequivalence studies detailed below, no new pharmacokinetic data is provided or required for these applications. The Marketing Authorisation Holder submitted the following bioequivalence studies to support the applications: Study 1 An open-label, randomised, single-dose, three-period, two-treatment, three-sequence, partial replicated, crossover, bioequivalence study comparing the test product Fixed Drug Formulation (FDC) of Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg tablet (Torrent Pharmaceuticals Limited) versus the reference product Stalevo tablets (containing Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg; Orion Corporation, Finland) in healthy human volunteers under fasting conditions. 24
25 Subjects were administered a single dose of either the test or reference product with 200 ml of water at room temperature after at least an 8-hour overnight fast, according to the randomisation schedule. Blood sampling was performed pre-dose and up to 18 hours post dose in each treatment period. A washout period of 7 days was kept between each consecutive dosing period. The pharmacokinetic results are presented below: Evaluation of bioequivalence Pharmacokinetic parameters (geometric Least Square Mean [LSM] ratios and confidence intervals [CI]) for levodopa, carbidopa and entacapone. AUC 0-t C max area under the plasma concentration-time curve from time zero to t hours maximum plasma concentration Bioequivalence Discussion and Conclusion The Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/Corr*) defines the confidence limits for ratio of geometric means for acceptance of bioequivalence as 80.00% to % for C max and AUC values. The intra-subject coefficient of variance (%ISCV) of the reference formulation for the C max of levodopa and carbidopa was < 30%; hence two one sided tests procedure was used for the bioequivalence claim for these analytes, with confidence limits of 80.00% to % set as criteria for bioequivalence. The intra-subject coefficient of variance (%ISCV) of the reference formulation for C max of entacapone was > 30%, hence the scaled average procedure was used for the bioequivalence claim for this analyte, with widen confidence limits of 70.84% to % set as criteria for bioequivalence. The results indicate that the bioequivalence criteria are met for levodopa and entacapone as the 25
26 AUC (0-t) and C max values for these analytes lie within acceptance limits. However the AUC (0-t) and C max values for carbidopa lie outside the acceptance limits and do not support the bioequivalence criteria. Hence, the data from this study do not support the claim that the applicant s test product is bioequivalent to the reference product under fasting conditions. As Study 1 did not demonstrate bioequivalence for carbidopa, the applicant also submitted the following studies: Study 2 An open-label, randomised, four-period, two-treatment, two-sequence, replicate, crossover, single-dose bioequivalence study comparing the test product FDC of Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg tablet (Torrent Pharmaceuticals Limited) versus the reference product Stalevo tablets containing Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg (Orion Corporation, Finland) in healthy human volunteers under fasting conditions. Subjects were administered a single dose of either the test or reference product with 200 ml of water at room temperature after at least an 8-hour overnight fast, according to the randomisation schedule. Blood sampling was performed pre-dose and up to 12 hours post dose in each treatment period. A washout period of 7 days was kept between each consecutive dosing period. The pharmacokinetic results are presented below: Evaluation of Bioequivalence Pharmacokinetic parameters (geometric Least Square Mean [LSM] ratios and confidence intervals [CI]) for levodopa, carbidopa and entacapone. AUC 0-t C max area under the plasma concentration-time curve from time zero to t hours maximum plasma concentration Bioequivalence Discussion and Conclusion The Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/Corr*) defines the confidence limits for ratio of geometric means for acceptance of bioequivalence as 80.00% to % for C max and AUC values. The intra-subject coefficient of variance (%ISCV) of the reference formulation for C max of levodopa and carbidopa were < 30%; hence the two one-sided tests procedure was used for the bioequivalence claim for these analytes, with confidence limits of 80.00% to % set as criteria for bioequivalence. The intra-subject coefficient of variance (%ISCV) of the reference formulation for C max of 26
27 entacapone was > 30%, hence the scaled average procedure was used for the bioequivalence claim for this analyte, with widen confidence limits of 73.61% to % set as criteria for bioequivalence. The results indicate that the bioequivalence criteria were met for levodopa, carbidopa and entacapone as the AUC (0-t) and C max values for these analytes lie within acceptance limits. Hence the data from this study support the claim that the applicant s test product Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg tablet is bioequivalent to the reference product Stalevo tablets (containing Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg; Orion Corporation, Finland) under fasting conditions. Study 3 An open-label, randomised, four-period, two-treatment, two-sequence, replicate, crossover, single-dose bioequivalence study comparing the test product, FDC of Levodopa 50 mg, Carbidopa 12.5 mg and Entacapone 200 mg tablet (Torrent Pharmaceuticals Limited) versus the reference product, Stalevo tablets containing Levodopa 50 mg, Carbidopa 12.5 mg and Entacapone 200 mg (Orion Corporation, Finland) in healthy human volunteers under fasting conditions. Subjects were administered a single dose of either the test or reference product with 200 ml of water at room temperature after at least an 8-hour overnight fast, according to the randomisation schedule. Blood sampling was performed pre-dose and up to 12 hours post dose in each treatment period. A washout period of 7 days was kept between each consecutive dosing period. The pharmacokinetic results are presented below: Evaluation of bioequivalence Pharmacokinetic parameters (geometric Least Square Mean [LSM] ratios and confidence intervals [CI] for levodopa, carbidopa and entacapone Pharmacokinetic parameter Geometric Mean Ratio Confidence Intervals Test/Ref Levodopa C max AUC 0-t Carbidopa C max AUC 0-t Entacapone C max AUC 0-t AUC 0-t C max area under the plasma concentration-time curve from time zero to t hours maximum plasma concentration Bioequivalence Discussion and Conclusion The Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/Corr*) defines the confidence limits for ratio of geometric means for acceptance of bioequivalence as 80.00% to % for C max and AUC values. The intra-subject coefficient of variance (%ISCV) of the reference formulation for the pharmacokinetic parameter of C max was 30% for levodopa and >30% for carbidopa and entacapone. Hence, for the bioequivalence claim, the two one-sided tests procedure was used for levodopa and scaled average bioequivalence procedure was used for carbidopa and entacapone for bioequivalence claim. 27
28 The results of the study demonstrate that the AUC (0-t) and C max values for levodopa, carbidopa and entacapone lie within the acceptance limits. Hence the data from this study support the claim that the applicant s test product (FDC of Levodopa 50 mg, Carbidopa 12.5 mg and Entacapone 200 mg tablet; Torrent Pharmaceuticals Limited) is bioequivalent to the reference product, Stalevo tablets (containing Levodopa 50mg, Carbidopa 12.5mg and Entacapone 200mg; Orion Corporation, Finland), under fasting conditions. Overall Bioequivalence Conclusion Based on the results from Study 2 and Study 3, bioequivalence has been demonstrated between the applicant s test products FDC of Levodopa 200mg, Carbidopa 50mg and Entacapone 200mg tablet and Levodopa 50mg, Carbidopa 12.5mg and Entacapone 200mg tablet and the reference products Stalevo tablets (containing Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg; Orion Corporation, Finland) and Stalevo tablets (containing Levodopa 50mg, Carbidopa 12.5mg and Entacapone 200mg; Orion Corporation, Finland), respectively, under fasting conditions. The results of the studies with FDC of Levodopa 200mg, Carbidopa 50mg and Entacapone 200mg tablet and Levodopa 50mg, Carbidopa 12.5mg and Entacapone 200mg tablet, can be extrapolated to other tablet strengths, 75 mg/18.75 mg/200 mg, 100 mg/25 mg/200 mg, 125 mg/31.25 mg /200 mg and 150 mg/37.5 mg/200 mg, according to conditions in Guideline on the Investigation of Bioequivalence CPMP/EWP/QWP/1401/98 Rev. 1/Corr*, section IV.2 Pharmacodynamics The clinical pharmacology of levodopa, carbidopa and entacapone is well-known. No new pharmacodynamic data were submitted and none are required for applications of this type. IV.3 Clinical Efficacy The clinical pharmacology of levodopa, carbidopa and entacapone is well-known. No new efficacy data are presented for these applications and none are required. IV.4 Clinical Safety With the exception of the data generated during the bioequivalence studies, no new safety data are presented for these applications and none are required. No new or unexpected safety issues arose during the bioequivalence studies. IV.5 Risk Management Plan The MAH has submitted a risk management plan, in accordance with the requirements of Directive 2001/83/EC as amended, describing the pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to Levodopa, Carbidopa and Entacapone Accord film-coated tablets. A summary of safety concerns in listed in the table below: 28
29 No additional risk minimisation activities were required beyond those included in the product information. IV.6 Clinical Expert Report (Clinical Overview) A clinical overview written by an appropriately qualified physician has been provided and is a suitable summary of the clinical aspects of the dossier. IV.7 Summary of Product Characteristics (SmPCs), Patient Information Leaflet (PIL) and Labels The SmPCs, PIL and labels are acceptable from a clinical perspective. The SmPCs are consistent with those for the innovator products. The PIL is consistent with the details in the SmPCs and in line with the current guidance. The labelling is in line with current guidance. 29
30 IV.8 Conclusion It is recommended that Marketing Authorisations are granted for Levodopa/Carbidopa/Entacapone Accord film-coated tablets, from a clinical point of view. V. USER CONSULTATION The package leaflet has been evaluated via a user consultation study in accordance with the requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The language used for the purpose of user testing the pack leaflet was English. The results show that the package leaflet meets the criteria for readability as set out in the Guideline on the readability of the label and package leaflet of medicinal products for human use. IV OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND RECOMMENDATION QUALITY The important quality characteristics of Levodopa/Carbidopa/Entacapone Accord 100 mg/25 mg/200 mg, 150 mg/37.5 mg/200 mg, 125 mg/31.25 mg/200 mg, 200 mg/50 mg/200 mg, 50mg/12.5 mg/200 mg and 75 mg/18.75 mg/200 mg film-coated tablets are well-defined and controlled. The specifications and batch analytical results indicate consistency from batch to batch. There are no outstanding quality issues that would have a negative impact on the benefit/risk balance. NON-CLINICAL No new non-clinical data were submitted. As the pharmacokinetics, pharmacodynamics and toxicology of levodopa, carbidopa and entacapone are well-known, no additional data were required. No new non-clinical data were submitted and none are required for applications of this type. EFFICACY With the exception of the bioequivalence studies, no new data were submitted and none are required for applications of this type. Bioequivalence has been demonstrated between the applicant s test products FDC of Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg tablet and Levodopa 50 mg, Carbidopa 12.5 mg and Entacapone 200 mg tablet and the reference products, Stalevo tablets containing Levodopa 200 mg, Carbidopa 50 mg and Entacapone 200 mg (Orion Corporation, Finland) and Stalevo tablets containing Levodopa 50 mg, Carbidopa 12.5 mg and Entacapone 200 mg (Orion Corporation, Finland), respectively, under fasting conditions. A biowaiver has been granted to the applicant s fixed drug combination 75 mg/18.75 mg/200 mg, 100 mg/25 mg/200 mg, 125 mg/31.25 mg/200 mg and 150 mg/37.5 mg/200 mg strength tablets based on data presented, in line with the current bioequivalence guideline. SAFETY With the exception of the safety data from the bioequivalence studies, no new data were submitted and none are required for these applications. As the safety profiles of levodopa, carbidopa and entacapone is well known, no additional safety data were required. No new or unexpected safety concerns arose from the bioequivalence studies. 30
31 PRODUCT LITERATURE The SmPCs and PIL are satisfactory, and consistent with those for the cross-reference products. The labelling complies with statutory requirements and is satisfactory. BENEFIT/RISK ASSESSMENT The quality of the products is acceptable, and no new non-clinical or clinical safety concerns have been identified. Extensive clinical experience with levodopa, carbidopa and entacapone is considered to have demonstrated the therapeutic value of the compounds. The benefit/risk balance is therefore considered to be positive. RECOMMENDATION The grant of Marketing Authorisations is recommended. 31
32 Annex 1 Table of content of the PAR update for MRP and DCP Steps taken after the initial procedure with an influence on the Public Assessment Report Scope Procedure number Product information affected Date of start of the procedure Date of end of procedure Approval/ non approval Assessment report attached Y/N (version) 32
Public Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Levodopa/Carbidopa/Entacapone Torrent 50 mg/12.5 mg/200 mg film-coated tablets Levodopa/Carbidopa/Entacapone Torrent, 75 mg/18.75 mg/200 mg film-coated
More informationLacidipine 2 mg Film-Coated Tablets PL 08553/0502. Lacidipine 4 mg Film-Coated Tablets PL 08553/0503. UK Public Assessment Report
Lacidipine 2 mg Film-Coated Tablets PL 08553/0502 Lacidipine 4 mg Film-Coated Tablets PL 08553/0503 UK Public Assessment Report TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 4 Steps taken
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure TELMISARTAN DR REDDY S 20 MG TABLETS TELMISARTAN DR REDDY S 40 MG TABLETS TELMISARTAN DR REDDY S 80 MG TABLETS (telmisartan) Procedure No: UK/H/5034/001-003/DC
More informationHYDROCORTISONE 10 MG TABLETS
HYDROCORTISONE 10 MG TABLETS (Hydrocortisone) PL 20072/0238 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 12 Steps taken after authorisation summary
More informationTRAMADOL HYDROCHLORIDE AND PARACETAMOL 37.5 MG/325 MG FILM-COATED TABLETS (tramadol hydrochloride and paracetamol ) PL 30684/0222 UKPAR
TRAMADOL HYDROCHLORIDE AND PARACETAMOL 37.5 MG/325 MG FILM-COATED TABLETS (tramadol hydrochloride and paracetamol ) PL 30684/0222 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 4
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Levetiracetam 250 mg film-coated tablets PL 36390/0168; UK/H/5630/001/DC Levetiracetam 500 mg film-coated tablets PL 36390/0169; UK/H/5630/002/DC Levetiracetam
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Olopatadine Zentiva 1 mg/ml eye drops, solution (olopatadine hydrochloride) Procedure No: UK Licence No: PL 17780/0568 Winthrop Pharmaceuticals UK Limited
More informationIbuprofen 200mg Soft Capsules PL 03105/0105 UKPAR
Ibuprofen 200mg Soft Capsules PL 03105/0105 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 4 Steps taken for assessment Page 13 Summary of Product Characteristics Page 14 Patient
More informationPL 17871/0208 UKPAR TABLE OF CONTENTS
Fultium-D 3 3,200 IU Capsules PL 17871/0208 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 4 Steps taken for assessment Page 11 Summary of Product Characteristics Page 12 Patient
More informationPublic Assessment Report
Public Assessment Report Decentralised Procedure Zoledronic Acid 4mg/5ml Concentrate for Solution for Infusion Procedure No: UK Licence No: PL 24598/0029 Noridem Enterprises Limited LAY SUMMARY On 25 January
More informationPublic Assessment Report. Decentralised Procedure. Sildenafil Dr. Reddy s 25, 50 and 100mg Filmcoated. Sildenafil citrate UK/H/4855/001-3/DC
Public Assessment Report Decentralised Procedure Sildenafil Dr. Reddy s 25, 50 and 100mg Filmcoated Sildenafil citrate UK licence no: PL 08553/0468-70 DR Reddy s Laboratories (UK) Limited 1 LAY SUMMARY
More informationPublic Assessment Report. Decentralised Procedure. Cefuroxime 250mg and 500mg film-coated tablets. Cefuroxime 500mg film-coated tablets
Public Assessment Report Decentralised Procedure Cefuroxime 250mg film-coated tablets Cefuroxime 500mg film-coated tablets Procedure No: UK Licence No: PL 35646/0020-0021 Alkem Pharma GmbH 1 LAY SUMMARY
More informationMIGRAINE RELIEF 342 MG FILM-COATED TABLETS PL 20154/0030 UKPAR TABLE OF CONTENTS
MIGRAINE RELIEF 342 MG FILM-COATED TABLETS PL 20154/0030 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 4 Steps taken for assessment Page 13 Steps taken after authorisation summary
More informationPublic Assessment Report UKPAR
Public Assessment Report UKPAR Amitriptyline 10 mg film-coated tablets Amitriptyline 25 mg film-coated tablets Amitriptyline 50 mg film-coated tablets (Amitriptyline hydrochloride) UK Licence No: PL 17907/0131-133
More informationPublic Assessment Report. Scientific discussion. Paracetamol Orifarm 500 mg film-coated tablets. (Paracetamol) DK/H/2271/001/DC.
Public Assessment Report Scientific discussion Paracetamol Orifarm 500 mg film-coated tablets (Paracetamol) DK/H/2271/001/DC 15 October 2014 This module reflects the scientific discussion for the approval
More informationPublic Assessment Report. Decentralised Procedure PARACETAMOL 1000 MG TABLETS. Procedure No: UK/H/5004/01/DC. UK Licence No: PL 18866/0060
Public Assessment Report Decentralised Procedure PARACETAMOL 1000 MG TABLETS Procedure No: UK Licence No: PL 18866/0060 Rockspring Healthcare Ltd LAY SUMMARY On 17 January 2013 the Medicines and Healthcare
More informationPublic Assessment Report. UK National Procedure. (colecalciferol) PL 16508/0047 PL 16508/0048. ProStrakan Ltd.
Public Assessment Report UK National Procedure STEXEROL-D 3 1,000 IU FILM-COATED TABLETS STEXEROL-D 3 25,000 IU FILM-COATED TABLETS (colecalciferol) PL 16508/0047 PL 16508/0048 ProStrakan Ltd. 1 LAY SUMMARY
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Paracetamol 500 mg effervescent tablets Procedure No: UK/H/5662/001-002/DC UK Licence No: PL 36390/0177-0178 Cipla (EU) Limited Lay Summary Paracetamol
More informationPublic Assessment Report
Public Assessment Report Decentralised Procedure Ibuprofen and phenylephrine hydrochloride 200mg/5mg film-coated tablets Procedure No: UK Licence No: PL 17780/0563 Winthrop Pharmaceuticals UK Limited LAY
More informationPublic Assessment Report. Decentralised Procedure. Cefadroxil 250 mg/5 ml granules for oral. (Cefadroxil monohydrate)
Public Assessment Report Decentralised Procedure Cefadroxil 250 mg/5 ml granules for oral suspension (Cefadroxil monohydrate) UK licence no: PL 34088/0033 Alkaloid-INT d.o.o. 1 Cefadroxil 250 mg/5 ml granules
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure BOSENTAN ZENTIVA 62.5 MG FILM-COATED TABLETS BOSENTAN ZENTIVA 125 MG FILM-COATED TABLETS BOSENTAN ZENTIVA 62.5 MG FILM-COATED TABLETS BOSENTAN ZENTIVA 125
More informationPublic Assessment Report. Scientific discussion. Desloracell 5 mg, film-coated tablet. (desloratadine) NL License RVG: 112807
Public Assessment Report Scientific discussion Desloracell 5 mg, film-coated tablet (desloratadine) NL License RVG: 112807 Date: 6 July 2015 This module reflects the scientific discussion for the approval
More informationPublic Assessment Report. UK National Procedure. Perindopril 2 mg Tablets. Perindopril 4 mg Tablets. Perindopril 8 mg Tablets PL 20075/0294-0296
Public Assessment Report UK National Procedure Perindopril 2 mg Tablets Perindopril 4 mg Tablets Perindopril 8 mg Tablets PL 20075/0294-0296 Accord Healthcare Limited 1 LAY SUMMARY This is a summary of
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure IMATINIB TEVA UK 100 MG FILM-COATED TABLETS IMATINIB TEVA UK 400 MG FILM-COATED TABLETS (imatinib mesilate) Procedure No: UK Licence No: PL 00289/1516-1517
More informationDonepezil hydrochloride 10 mg film-coated tablets PL 19156/0130
Donepezil hydrochloride 10 mg film-coated tablets PL 19156/0130 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific Discussion Page 4 Steps Taken for Assessment Page 12 Summary of Product Characteristics
More informationMemantine hydrochloride 20 mg film-coated tablets PL 17907/0291
Memantine hydrochloride 20 mg film-coated tablets PL 17907/0291 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific Discussion Page 5 Steps Taken for Assessment Page 13 Summary of Product Characteristics
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Amlodipine Pfizer 5 mg tablets Amlodipine Pfizer 10 mg tablets Amlodipine Pfizer 5 mg hard capsules Amlodipine Pfizer 10 mg hard capsules Procedure No:
More informationPublic Assessment Report. Decentralised Procedure. Ipravent CFC-Free Inhaler 20 micrograms per actuation pressurised inhalation, solution
Public Assessment Report Decentralised Procedure Ipravent CFC-Free Inhaler 20 micrograms per actuation pressurised inhalation, solution (ipratropium bromide monohydrate) Procedure No: UK Licence No: PL
More informationPublic Assessment Report Scientific discussion. Levetiracetam Krka (Levetiracetam) SE/H/1067/01-04/DC
Public Assessment Report Scientific discussion Levetiracetam Krka (Levetiracetam) SE/H/1067/01-04/DC This module reflects the scientific discussion for the approval of Levetiracetam Krka. The procedure
More informationPublic Assessment Report. Decentralised Procedure. Tenofovir Zentiva 245 mg Film-coated Tablets. Tenofovir disoproxil fumarate UK/H/4970/001/DC
Public Assessment Report Decentralised Procedure Tenofovir Zentiva 245 mg Film-coated Tablets Tenofovir disoproxil fumarate UK licence no: PL 17780/0573 Winthrop Pharmaceuticals UK Limited 1 LAY SUMMARY
More informationANASTROZOLE 1 MG FILM-COATED TABLETS. (Anastrozole) PL 40378/0123 UKPAR TABLE OF CONTENTS
ANASTROZOLE 1 MG FILM-COATED TABLETS (Anastrozole) PL 40378/0123 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 11 Summary of Product Characteristics
More informationPublic Assessment Report. Decentralised Procedure. PAR Bisoprolol 1.25 mg, 2.5 mg, 3.75 mg, 5 mg, 7.5 mg and 10 mg film-coated tabs
PAR Bisoprolol 1.25 mg, 2.5 mg, 3.75 mg, 5 mg, 7.5 mg and 10 mg film-coated tabs Public Assessment Report Decentralised Procedure Bisoprolol 1.25 mg, 2.5 mg, 3.75 mg, 5 mg, 7.5 mg and 10 mg film-coated
More informationFexofenadine Hydrochloride 120 mg Film-coated Tablets Fexofenadine Hydrochloride 180 mg Film-coated Tablets PL 36390/0053-4 UKPAR TABLE OF CONTENTS
Fexofenadine Hydrochloride 120 mg Film-coated Tablets Fexofenadine Hydrochloride 180 mg Film-coated Tablets PL 36390/0053-4 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 5 Steps
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure LANSOPRAZOLE 15 MG AND 30 MG ORODISPERSIBLE TABLETS (lansoprazole) Procedure No: UK Licence No: PL 35507/0118-0119 Lupin (Europe) Limited LAY SUMMARY Lansoprazole
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Atorvastatin 10 mg film-coated Tablets Atorvastatin 20 mg film-coated Tablets Atorvastatin 40 mg film-coated Tablets Atorvastatin 80 mg film-coated Tablets
More informationPublic Assessment Report UKPAR. Levonorgestrel 1.5 mg tablet. (levonorgestrel). UK Licence No: PL 41947/0006. ELC Group s.r.o.
Public Assessment Report UKPAR Levonorgestrel 1.5 mg tablet (levonorgestrel). UK Licence No: PL 41947/0006 ELC Group s.r.o. 1 LAY SUMMARY Levonorgestrel 1.5 mg tablet (Levonorgestrel, tablet, 1.5 mg) This
More informationSummary Public Assessment Report. Generics
Summary Public Assessment Report Generics 875 mg + 125 mg, Film-coated tablets (Amoxicillin Trihydrate + Potassium Clavulanate) Date: 29-12-2014 1/7 Summary Public Assessment Report Generics Amoxicillin
More informationPublic Assessment Report
Public Assessment Report Decentralised Procedure Alendronic Acid and Calcium/Cholecalciferol 70+1000mg/880IU Film-coated Tablets+Effervescent Tablets Procedure No: UK Licence No: PL 04416/1162-4 Sandoz
More informationSummary Public Assessment Report. Generics. Amoxicilina + Ácido Clavulânico Ranbaxy,
Summary Public Assessment Report Generics Amoxicilina + Ácido Clavulânico Ranbaxy 875 mg + 125 mg, Film-coated tablets (Amoxicillin Trihydrate + Potassium Clavulanate) Date: 29-12-2014 1/7 Summary Public
More informationOMEPRAZOLE 10 MG, 20 MG AND 40 MG GASTRO-RESISTANT HARD CAPSULES. (omeprazole)
OMEPRAZOLE 10 MG, 20 MG AND 40 MG GASTRO-RESISTANT HARD CAPSULES (omeprazole) PL 36884/0001, PL 36884/0002, PL 36884/0003, PL 36884/0004, PL 36884/0005 AND PL 36884/0006 UKPAR TABLE OF CONTENTS Lay Summary
More informationPublic Assessment Report. Decentralised Procedure. CosmoCol Half 6.9 g, powder for oral solution CosmoCol Paediatric 6.9 g, powder for oral solution
Public Assessment Report Decentralised Procedure CosmoCol Half 6.9 g, powder for oral solution CosmoCol Paediatric 6.9 g, powder for oral solution (Macrogol, sodium chloride, sodium hydrogen carbonate
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure FOSFOMYCIN 3G GRANULES FOR ORAL SOLUTION Procedure No: UK Licence No: PL 31513/0007 Temapharm Sp. z.o.o. LAY SUMMARY On 17 April 2013, Czech Republic, Estonia,
More informationOmeprazole 20 mg gastro-resistant tablets PL 14017/0277
Omeprazole 20 mg gastro-resistant tablets PL 14017/0277 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific Discussion Page 4 Steps Taken for Assessment Page 11 Steps Taken After Initial Authorisation
More informationRILUZOLE LUPIN 50 MG FILM-COATED TABLETS PL 35507/0120 UKPAR TABLE OF CONTENTS
RILUZOLE LUPIN 50 MG FILM-COATED TABLETS PL 35507/0120 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 9 Steps taken after authorisation summary
More informationAciclovir 200mg Tablets Aciclovir 400mg Tablets Aciclovir 800mg Tablets PL 29831/0517 PL 29831/0518 PL 29831/0519 UKPAR
Aciclovir 200mg Tablets Aciclovir 400mg Tablets Aciclovir 800mg Tablets PL 29831/0517 PL 29831/0518 PL 29831/0519 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for
More informationAscorbic Acid 50 mg Tablets. Ascorbic Acid 100 mg Tablets. Ascorbic Acid 200 mg Tablets. Ascorbic Acid 500 mg Tablets PL 20416/0286 PL 20416/0287
Ascorbic Acid 50 mg Tablets Ascorbic Acid 100 mg Tablets Ascorbic Acid 200 mg Tablets Ascorbic Acid 500 mg Tablets PL 20416/0286 PL 20416/0287 PL 20416/0288 PL 20416/0289 UKPAR TABLE OF CONTENTS Lay Summary
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Linezolid 2 mg/ml solution for infusion Linezolid 600mg film coated tablets Linezolid 100mg/5ml granules for oral suspension Procedure No: UK Licence No:
More informationPublic Assessment Report. Scientific discussion. Calcium and Vitamine D3 Alpex 1000 mg/880 IE, effervescent granules
Public Assessment Report Scientific discussion Calcium and Vitamine D3 Alpex 1000 mg/880 IE, effervescent granules (calcium carbonate and cholecalciferol) NL License RVG: 111783 Date: 12 March 2015 This
More informationPublic Assessment Report. Scientific discussion. Atorvastatin DK/H/1744/001-004/DC
Public Assessment Report Scientific discussion Atorvastatin Orifarm 10 mg 20 mg, 40 mg and 80 mg film-coated tablets Atorvastatin DK/H/1744/001-004/DC This module reflects the scientific discussion for
More informationPublic Assessment Report. Decentralised Procedure. Omega 3-acid-ethyl esters 1000mg Soft Capsules. Omega-3-acid ethyl esters 90
Public Assessment Report Decentralised Procedure Omega 3-acid-ethyl esters 1000mg Soft Capsules Omega-3-acid ethyl esters 90 Procedure No: UK Licence No: PL 00289/1756 and PL 00289/1778-80 Teva UK Limited
More informationMACROGOL COMPOUND ORAL POWDER (sodium chloride, sodium hydrogen carbonate, potassium chloride, macrogol 3350) PL 33579/0001 UKPAR TABLE OF CONTENTS
MACROGOL COMPOUND ORAL POWDER (sodium chloride, sodium hydrogen carbonate, potassium chloride, macrogol 3350) PL 33579/0001 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 4 Steps
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure PERRIGO PARACETAMOL/GUAIFENESIN/PHENYLEPHRINE HYDROCHLORIDE 500 MG/200 MG/10 MG POWDER FOR ORAL SOLUTION UK Licence No: PL 12063/0118 WRAFTON LABORATORIES
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure TRIAMCINOLONE HEXACETONIDE 20 MG/ML SUSPENSION FOR INJECTION (triamcinolone hexacetonide) Procedure No: UK Licence No: PL 17509/0061 Intrapharm Laboratories
More informationPublic Assessment Report. Decentralised Procedure. Alimemazine tartrate 7.5mg/5ml Syrup. Alimemazine tartrate 30mg/5ml Syrup
Public Assessment Report Decentralised Procedure Alimemazine tartrate 7.5mg/5ml Syrup Alimemazine tartrate 30mg/5ml Syrup Procedure No: UK Licence No: PL 41830/0029-0030 NRIM Limited 1 LAY SUMMARY Alimemazine
More informationSTREPSILS BLACKCURRANT FLAVOUR LOZENGES STREPSILS DRY & SORE THROAT BLACKCURRANT FLAVOUR LOZENGES
STREPSILS BLACKCURRANT FLAVOUR LOZENGES STREPSILS DRY & SORE THROAT BLACKCURRANT FLAVOUR LOZENGES (amylmetacresol, 2,4-dichlorobenzyl alcohol, ascorbic acid and sodium ascorbate) PL 00063/0692 UKPAR TABLE
More informationLevonorgestrel/Ethinylestradiol 150/30 Microgram Coated Tablets PL 20117/0044
Levonorgestrel/Ethinylestradiol 150/30 Microgram Coated Tablets PL 20117/0044 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 11 Summary of Product
More informationMontelukast 10mg film-coated tablets PL 17907/0474
Montelukast 10mg film-coated tablets PL 17907/0474 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific Discussion Page 4 Steps Taken for Assessment Page 11 Steps Taken After Initial Authorisation Page
More informationFRENCH AGENCY FOR VETERINARY MEDICINAL PRODUCTS DECENTRALISED PROCEDURE PUBLICLY AVAILABLE ASSESSMENT REPORT FOR A VETERINARY MEDICINAL PRODUCT
FRENCH AGENCY FOR VETERINARY MEDICINAL PRODUCTS DECENTRALISED PROCEDURE FOR A VETERINARY MEDICINAL PRODUCT VIRBAKOR 20 mg film-coated tablet for dogs Date: 03/11/2014 French agency for food, environnemental
More informationPublic Assessment Report Scientific discussion. Amitriptylin Abcur (amitriptyline hydrochloride) Asp no : 2013-0678 2013-0679 2013-0680
Public Assessment Report Scientific discussion Amitriptylin Abcur (amitriptyline hydrochloride) Asp no : 2013-0678 2013-0679 2013-0680 This module reflects the scientific discussion for the approval of
More informationLEMSIP MAX DAY & NIGHT COLD & FLU RELIEF CAPSULES. (paracetamol, caffeine and phenylephrine hydrochloride)
LEMSIP MAX DAY & NIGHT COLD & FLU RELIEF CAPSULES (paracetamol, caffeine and phenylephrine hydrochloride) PL 00063/0529 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific Discussion Page 5 Summary of
More informationPublic Assessment Report. Decentralised Procedure. Omeprazole 10mg Gastro-resistant Capsules, hard. Omeprazole 20mg Gastro-resistant Capsules, hard
Public Assessment Report Decentralised Procedure Omeprazole 10mg Gastro-resistant Capsules, hard Omeprazole 20mg Gastro-resistant Capsules, hard Omeprazole 40mg Gastro-resistant Capsules, hard (UK/H/4423/001-003/DC)
More informationCompilation of individual product-specific guidance on demonstration of bioequivalence
17 December 2014 EMA/CHMP/736403/2014 Committee for Medicinal Products for Human Use (CHMP) Compilation of individual product-specific guidance on demonstration of bioequivalence Initial batch of individual
More informationDecentralised Procedure. Public Assessment Report
Bundesinstitut für Arzneimittel und Medizinprodukte Decentralised Procedure Public Assessment Report ben-u-ron direkt Erdbeer/Vanille 250/500 mg Granulat in Beuteln ben-u-ron direkt Cappuccino 500/1000
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Opticrom Allergy Single Dose 2% w/v Eye Drops, Solution (sodium cromoglicate) Procedure No: UK Licence No: PL 04425/0688 Aventis Pharma Limited (T/A Sanofi-aventis
More informationBeclometasone Dipropionate 50 micrograms per spray Aqueous Nasal Spray PL 16431/0178
Beclometasone Dipropionate 50 micrograms per spray Aqueous Nasal Spray PL 16431/0178 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific Discussion Page 5 Steps Taken for Assessment Page 11 Steps Taken
More informationPublic Assessment Report. Scientific discussion. Paracetamol Alternova 500 mg, 650 mg, 1 g (paracetamol) Asp no: 2012-0005, 2012-0006, 2012-0007
Public Assessment Report Scientific discussion Paracetamol Alternova 500 mg, 650 mg, 1 g (paracetamol) Asp no: 2012-0005, 2012-0006, 2012-0007 Applicant: E Consult ApS, Denmark This module reflects the
More informationHypromellose Eye Drops BP 0.3% w/v PL 23097/0006
Hypromellose Eye Drops BP 0.3% w/v PL 23097/0006 UKPAR TABLE OF CONTENTS Lay summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 9 Summary of product characteristics Page 10 Patient
More informationPublic Assessment Report. Decentralised Procedure
Public Assessment Report Decentralised Procedure Linezolid Pfizer 2 mg/ml Solution for Infusion Linezolid Pfizer 100 mg/5 ml Granules for Oral Suspension Procedure No: UK/H/5515/001-003/DC UK Licence No:
More informationPublic Assessment Report Scientific discussion. Prednisolon Pilum (prednisolone) Asp no: 2013-0498
Public Assessment Report Scientific discussion Prednisolon Pilum (prednisolone) Asp no: 2013-0498 This module reflects the scientific discussion for the approval of Prednisolon Pilum. The procedure was
More informationPublic Assessment Report Scientific discussion. Tenofovir disoproxil Teva (tenofovir disoproxil) SE/H/1432/01/DC
Public Assessment Report Scientific discussion Tenofovir disoproxil Teva (tenofovir disoproxil) SE/H/1432/01/DC This module reflects the scientific discussion for the approval of Tenofovir disoproxil Teva.
More informationPublic Assessment Report. Scientific discussion. Atorvastatine Glob 10 mg,20 mg, 40 mg, and 80 mg, film-coated tablets
Public Assessment Report Scientific discussion Atorvastatine Glob 10 mg,20 mg, 40 mg, and 80 mg, film-coated tablets (Atorvastatin calcium trihydrate) NL/H/2994/001-004/DC Date: 16 March 2015 This module
More informationPublic Assessment Report. Scientific discussion. Paracetamol Apofri 500 mg (paracetamol) Asp no: 2012-0676. Applicant: E Consult ApS, Denmark
Public Assessment Report Scientific discussion Paracetamol Apofri 500 mg (paracetamol) Asp no: 2012-0676 Applicant: E Consult ApS, Denmark This module reflects the scientific discussion for the approval
More informationPublic Assessment Report. Scientific discussion. Lercanidipinhydrochlorid Sandoz 10 mg and 20 mg film-coated tablets. (Lercanidipine hydrochloride)
Public Assessment Report Scientific discussion Lercanidipinydroclorid Sandoz 10 mg and 20 mg film-coated tablets (Lercanidipine ydrocloride) DK/H/2360/001-002/DC 1 December 2015 Tis module reflects te
More informationCETIRIZINE DIHYDROCHLORIDE 10MG FILM-COATED TABLETS PL 40378/0140-1 UKPAR TABLE OF CONTENTS
CETIRIZINE DIHYDROCHLORIDE 10MG FILM-COATED TABLETS PL 40378/0140-1 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 8 Steps taken after authorisation
More informationPublic Assessment Report. (Budesonide) PL 17901/0254. AstraZeneca UK Ltd
Public Assessment Report Rhinocort Hay Fever 64 micrograms, Nasal Spray (Budesonide) PL 17901/0254 AstraZeneca UK Ltd 1 LAY SUMMARY Rhinocort Hay Fever 64 micrograms, Nasal Spray (Budesonide) This is a
More informationPhynova Joint and Muscle Relief Tablets THR 41783/0001 UKPAR
Phynova Joint and Muscle Relief Tablets THR 41783/0001 UKPAR TABLE OF CONTENTS Lay summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 12 Summary of Product Characteristics Page
More informationPublic Assessment Report Scientific discussion. Prednisolon Alternova (previous Prednisolon E Consult) (prednisolone) Asp no: 2011-0921
Public Assessment Report Scientific discussion Prednisolon Alternova (previous Prednisolon E Consult) (prednisolone) Asp no: 2011-0921 This module reflects the scientific discussion for the approval of
More informationPublic Assessment Report. Decentralised Procedure. PAR Flucloxacillin 250 mg & 500 mg Capsules. Flucloxacillin 500 mg Capsules.
Public Assessment Report Decentralised Procedure Flucloxacillin 250 mg Capsules Flucloxacillin 500 mg Capsules (flucloxacillin) Procedure No: UK/H/1101/001-002/DC UK Licence No: PL 21880/0017-0018 Medreich
More informationPublic Assessment Report Scientific discussion. Prednisolon mibe (prednisolone acetate) SE/H/1317/01/DC
Public Assessment Report Scientific discussion Prednisolon mibe (prednisolone acetate) SE/H/1317/01/DC This module reflects the scientific discussion for the approval of Prednisolon mibe. The procedure
More informationDecentralised Procedure. Public Assessment Report
Decentralised Procedure Public Assessment Report Articainhydrochlorid mit Epinephrin Pierrel 40 mg/ml + 0.01 mg/ml Injektionslösung Articainhydrochlorid mit Epinephrin Pierrel 40 mg/ml + 0.005 mg/ml Injektionslösung
More informationCETRABEN ORIGINAL EMOLLIENT CREAM (PL 06831/0262) UKPAR TABLE OF CONTENTS
CETRABEN ORIGINAL EMOLLIENT CREAM (PL 06831/0262) UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 12 Steps taken after authorisation summary Page
More informationPublic Assessment Report. Scientific discussion. Ramipril Teva 1.25 mg, 2.5 mg, 5 mg and 10 mg tablets Ramipril DK/H/2130/001-004/DC.
Public Assessment Report Scientific discussion Ramipril Teva 1.25 mg, 2.5 mg, 5 mg and 10 mg tablets Ramipril DK/H/2130/001-004/DC 3 April 2014 Tis module reflects te scientific discussion for te approval
More informationPublic Assessment Report
Public Assessment Report Decentralised Procedure DILACORT 2.5 MG GASTRO-RESISTANT TABLETS DILACORT 5 MG GASTRO-RESISTANT TABLETS (prednisolone) Procedure No: UK Licence No: PL 17507/0186-7 Auden McKenzie
More informationUrostemol Men capsules THR 02855/0240
Urostemol Men capsules THR 02855/0240 UKPAR TABLE OF CONTENTS Lay summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 14 Steps taken after initial registration Page 15 Summary of
More informationPublic Assessment Report. Scientific discussion
Public Assessment Report Scientific discussion 1) Risedronat Actavis 5 mg Filmtabletten, 30 mg Filmtabletten, 35 mg einmal wöchentlich Filmtabletten 2) Bifodron 5 mg Filmtabletten, 30 mg Filmtabletten,
More informationNEUROTONE THR 00904/0005 UKPAR
NEUROTONE THR 00904/0005 UKPAR TABLE OF CONTENTS Lay summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 10 Summary of Product Characteristics Page 11 Product Information Leaflet
More informationDecentralised Procedure. Public Assessment Report. Paracetamol-ratiopharm 10 mg/ml Infusionslösung Paracetamol DE/H/1908/001/DC
Bundesinstitut für Arzneimittel und Medizinprodukte Decentralised Procedure Public Assessment Report Paracetamol-ratiopharm 10 mg/ml Infusionslösung Paracetamol DE/H/1908/001/DC Applicant: TEVA Pharma
More informationHow To Market Pantoprazol Beximco
Public Assessment Report Scientific discussion Pantoprazol Beximco 20 mg and 40 mg, gastro-resistant tablets (pantoprazole) NL/H/2751/001-002/DC Date: 27 August 2014 This module reflects the scientific
More informationPublic Assessment Report. Scientific discussion. Apotel 10 mg/ml, solution for infusion. (paracetamol) NL/H/2857/001/DC
Public Assessment Report Scientific discussion Apotel 10 mg/ml, solution for infusion (paracetamol) NL/H/2857/001/DC Date: 16 December 2014 This module reflects the scientific discussion for the approval
More informationPUBLIC ASSESSMENT REPORT Scientific Discussion. Perindopril arginine Amlodipine FR/H/325-326-327/01-04/DC. Applicant: Servier
Direction de l Evaluation des Médicaments et des Produits Biologiques PUBLIC ASSESSMENT REPORT Scientific Discussion COVERAM PERINDOPRIL ARGININE - AMLODIPINE SERVIER PERINDOPRIL ARGININE AMLODIPINE BIOPHARMA
More informationPublic Assessment Report. Scientific discussion. Ibuprofen Sandoz 200 mg and 400 mg, capsules, soft. (ibuprofen) NL/H/2810/001-002/MR
Public Assessment Report Scientific discussion Ibuprofen Sandoz 200 mg and 400 mg, capsules, soft (ibuprofen) 001-002/MR Date: 28 January 2016 This module reflects the scientific discussion for the approval
More informationDEXTROMETHORPHAN HYDROBROMIDE 10MG/5ML ORAL SOLUTION PL 17907/0314
DEXTROMETHORPHAN HYDROBROMIDE 10MG/5ML ORAL SOLUTION PL 17907/0314 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 10 Summary of Product Characteristics
More informationUKPAR Goodnight THR 00904/0003. Goodnight THR 00904/0003 UKPAR TABLE OF CONTENTS. Lay Summary Page 2. Scientific discussion Page 3
Goodnight THR 00904/0003 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 12 Steps taken after authorisation Page 13 Summary of Product Characteristics
More informationMucodyne-Clear 250 mg/5 ml Syrup PL 04425/0665
Mucodyne-Clear 250 mg/5 ml Syrup PL 04425/0665 UKPAR TABLE OF CONTENTS Lay summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 9 Summary of product characteristics Page 10 Patient
More informationClinical Study Synopsis for Public Disclosure
abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of the clinical
More informationArnicare Arnica 30c pillules NR 01175/0181 UKPAR
Arnicare Arnica 30c pillules NR 01175/0181 UKPAR TABLE OF CONTENTS Lay summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 11 Summary of product characteristics Page 12 Product
More informationPublic Assessment Report. Decentralised Procedure. Diclopram 75 mg/ 20 mg modified-release hard capsules. (Diclofenac sodium and omeprazole)
Public Assessment Report Decentralised Procedure Diclopram 75 mg/ 20 mg modified-release hard capsules (Diclofenac sodium and omeprazole) Procedure No: UK Licence No: PL 33616/0002 Pharmaswiss Česká republika
More informationCollege ter Beoordeling van Geneesmiddelen (CBG) Medicines Evaluation Board (MEB) Graadt van Roggenweg 500 3531 AH Utrecht The Netherlands
MEB agency / Veterinary Medicinal Products Unit The Netherlands C B G M E B College ter Beoordeling van Geneesmiddelen (CBG) Medicines Evaluation Board (MEB) Graadt van Roggenweg 500 3531 AH Utrecht The
More informationGinkgoforce Ginkgo biloba tablets THR 13668/0016 UKPAR
Ginkgoforce Ginkgo biloba tablets THR 13668/0016 UKPAR TABLE OF CONTENTS Lay summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 13 Summary of product characteristics Page 14 Product
More informationGuidance for Industry
Guidance for Industry Food-Effect Bioavailability and Fed Bioequivalence Studies U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER)
More information